Bulk and Surface Acoustic Wave Biosensors for Milk Analysis

Milk and dairy products are common foods and, therefore, are subject to regular controls. Such controls cover both the identification and quantification of specific components and the determination of physical parameters. Components include the usual milk ingredients, mainly carbohydrates, proteins, and fat, and any impurities that may be present. The latter range from small molecules, such as drug residues, to large molecules, e.g., protein-based toxins, to pathogenic microorganisms. Physical parameters of interest include viscosity as an indicator of milk gelation. Bulk and surface acoustic wave sensors, such as quartz crystal microbalance (QCM) and surface acoustic wave (SAW) devices, can principally be used for both types of analysis, with the actual application mainly depending on the device coating and the test format. This review summarizes the achievements of acoustic sensor devices used for milk analysis applications, including the determination of physical liquid parameters and the detection of low- and high-molecular-weight analytes and microorganisms. It is shown how the various requirements resulting from the respective analytes and the complex sample matrix are addressed, and to what extent the analytical demands, e.g., with regard to legal limits, are met

Modeling, characterization and integration of thin film resonator microsensors

There is an increasing demand by using smart and miniaturized microsensors and microtransducers in the areas of automobile, environment Science and analytical chemistry. Thin film microresonators (TFRs), meriting from their small size, higher sensitivity and compatibility with VLSI process, have being investigated as microsensors. Gas or vapor absorbed species, or contacted liquids may perturb resonator mechanical, electrical and piezoelectric properties. In this dissertation, a coupled wave theory is presented and applied to analyze acoustic wave propagation phenomena both in TFR-solid and TFR-liquid phases. A two-dimensional analysis is implemented to compare with a one-dimensional model and experimental results. The analysis and characterization of polymer-coated TFR sensors are investigated, along with sensitivity and detection limit analysis. The experimental characterization of liquid-coated TFR sensors are also then investigated and discussed. In order to minimize temperature-induced drift and other possible geometrical and material mismatch, the design and implementation of a TFR microsensor array in which a differential approach was proposed have been demonstrated. The major challenge in the array design is to evaluate the wave crosstalks between individual TFRs and to investigate film mechanical strength in order to host multi-TFRs on a single substrate dice. General analytic EM design rules and numerical methods are used to model lateral wave coupling and assist the design of process masks. The processing and electrical measurements of TFR arrays are then investigated. The implementation and experimental characterization of a TFR polymer sensor array are finally presented and discussed

Probing multivalent particle–surface interactions using a quartz crystal resonator

The rise in market-approved cellular therapies demands for advancements in process analytical technology (PAT) capable of fulfilling the requirements of this new industry. Unlike conventional biopharmaceuticals, cell-based therapies (CBT) are complex “live” products, with a high degree of inherent biological variability. This exacerbates the need for in-process monitoring and control of critical product attributes, in order to guarantee safety, efficacious and continuous supply of this CBT. There are therefore mutual industrial and regulatory motivations for high throughput, non-invasive and non-destructive sensors, amenable to integration in an enclosed automated cell culture system. While a plethora of analytical methods is available for direct characterization of cellular parameters, only a few satisfy the requirements for online quality monitoring of industrial-scale bioprocesses. [Continues.

System for monitoring and controlling unit operations that include distillation

Fluid sensor methods and systems adapted for monitoring and/or controlling distillation operations in fluidic systems, such as bath distillation operations or continuous distillation operations, are disclosed. Preferred embodiments are directed to process monitoring and/or process control for unit operations involving endpoint determination of a distillation, for example, as applied to a liquid-component-switching operation (e.g., a solvent switehing operation), a liquid-liquid separation operation, a solute concentration operation, a dispersed- phase concentration operation, among others

A Monolithic Spiral Coil Acoustic Transduction Sensor for Chemical and Biological Analytes

Acoustic wave sensor platforms typically consist of piezoelectric materials in which bulk or surface acoustic waves are excited by metallic transducers deposited on the sensing surface of the platform. This type of transduction has limitations. In particular the transducer may limit the type of sensing film that can be used or analyte that can be measured and limit the frequency of operation of the sensor. In this work a novel method of exciting high frequency bulk acoustic waves in piezoelectric sensor platforms has been explored. This technique consists of applying time varying electromagnetic fields to the sensor platform using an antenna in order to excite high order harmonic acoustic waves. This configuration is known as a Monolithic Spiral Coil Acoustic Transduction (MSCAT) device. This technique offers benefits such as a bare sensing surface that allows for the detection of both mechanical and electrical property changes in the film or analyte and is capable of operating at high frequencies by exciting high order harmonics (\u3e 99th harmonic) in the substrate. The antenna configurations have been experimentally and theoretically examined and an understanding of how these electric fields excite the acoustic waves in the substrate has been developed. Finally, the MSCAT sensor platform was used to detect real world chemical and biological analytes and found in many cases to be superior to other bulk acoustic wave sensor platforms

Theoretical and experimental development of a ZnO-based laterally excited thickness shear mode acoustic wave immunosensor for cancer biomarker detection

The object of this thesis research was to develop and characterize a new type of acoustic biosensor - a ZnO-based laterally excited thickness shear mode (TSM) resonator in a solidly mounted configuration. The first specific aim of the research was to develop the theoretical underpinnings of the acoustic wave propagation in ZnO. Theoretical calculations were carried out by solving the piezoelectrically stiffened Christoffel equation to elucidate the acoustic modes that are excited through lateral excitation of a ZnO stack. A finite element model was developed to confirm the calculations and investigate the electric field orientation and density for various electrode configurations. A proof of concept study was also carried out using a Quartz Crystal Microbalance device to investigate the application of thickness shear mode resonators to cancer biomarker detection in complex media. The results helped to provide a firm foundation for the design of new gravimetric sensors with enhanced capabilities. The second specific aim was to design and fabricate arrays of multiple laterally excited TSM devices and fully characterize their electrical properties. The solidly mounted resonator configuration was developed for the ZnO-based devices through theoretical calculations and experimentation. A functional mirror comprised of W and SiO2 was implemented in development of the TSM resonators. The devices were fabricated and tested for values of interest such as Q, and electromechanical coupling (K2) as well as their ability to operate in liquids. The third specific aim was to investigate the optimal surface chemistry scheme for linking the antibody layer to the ZnO device surface. Crosslinking schemes involving organosilane molecules and a phosphonic acid were compared for immobilizing antibodies to the surface of the ZnO. Results indicate that the thiol-terminated organosilane provides high antibody surface coverage and uniformity and is an excellent candidate for planar ZnO functionalization. The fourth and final specific aim was to investigate the sensitivity of the acoustic immunosensors to potential diagnostic biomarkers. Initial tests were performed in buffer spiked with varying concentrations of the purified target antigen to develop a dose-response curve for the detection of mesothelin-rFc. Subsequent tests were carried out in prostate cancer cell line conditioned medium for the detection of PSA. The results of the experiments establish the operation of the devices in complex media, and indicate that the acoustic sensors are sensitive enough for the detection of biomolecular targets at clinically relevant concentrations.Ph.D.Committee Chair: William D Hunt; Committee Member: Bruno Frazier; Committee Member: Dale Edmondson; Committee Member: Marie Csete; Committee Member: Peter Edmonson; Committee Member: Ruth O'Rega

A Lateral Field Excited Thin Film Bulk Acoustic Wave Sensor

Medical and environmental needs have served as a catalyst for the development of sensors that can probe the molecular level and below. This study addresses the practicality of highly sensitive aluminum nitride (AlN) thin film bulk acoustic wave resonators (FBARs) as sensors from theoretical and experimental points of view. Theoretically, COMSOL Multiphysics simulations predict that lateral field excitation of AlN produces an electric field perpendicular to the c-axis, with the electrical energy density being concentrated in the active area of the sensor. An analysis of the piezoelectrically stiffened Christoffel equation shows that the shear mode can be excited by an applied electric field in the x − y plane. Several thin films were deposited on various substrates such as borosilicate glass, silicon, sapphire, and fused silica using RF reactive magnetron sputtering and e-beam evaporation. To characterize film structure and composition, x- ray diffraction and x-ray photoelectron spectroscopy were used. An Agilent network analyzer was used to assess the performance of the sensor in air and water. In the most successful case, c-axis AlN films with a FWHM of 1.5 degrees were fabricated with quality factors between 33-36 in air and water. The magnitude of the admittance did not change appreciably when the film was exposed to water, indicating a shear mode was excited. Overall, a building block to a realizable AlN sensor was established

Applied Measurement Systems

Measurement is a multidisciplinary experimental science. Measurement systems synergistically blend science, engineering and statistical methods to provide fundamental data for research, design and development, control of processes and operations, and facilitate safe and economic performance of systems. In recent years, measuring techniques have expanded rapidly and gained maturity, through extensive research activities and hardware advancements. With individual chapters authored by eminent professionals in their respective topics, Applied Measurement Systems attempts to provide a comprehensive presentation and in-depth guidance on some of the key applied and advanced topics in measurements for scientists, engineers and educators